TY - JOUR
T1 - Using all-atom simulations in explicit solvent to study aggregation of amphipathic peptides into amyloid-like fibrils
AU - Jalali, Sharareh
AU - Yang, Yanxing
AU - Mahmoudinobar, Farbod
AU - Singh, Shaneen M.
AU - Nilsson, Bradley L.
AU - Dias, Cristiano
N1 - Funding Information:
This work supported by the National Science Foundation under Grant Nos. CHE-1904364 and CHE-1904528. Computational resources were provided by Academic and Research Computing Systems (ARCS) at the New Jersey Institute of Technology and by the Pittsburgh Supercomputing Center (PSC). Anton 2 at PSC is supported by the National Institute of General Medical Sciences of the National Institute of Health under Award Number R01GM116961. The Anton 2 machine at PSC was generously made available by D.E. Shaw Research.
Funding Information:
This work supported by the National Science Foundation under Grant Nos. CHE-1904364 and CHE-1904528. Computational resources were provided by Academic and Research Computing Systems (ARCS) at the New Jersey Institute of Technology and by the Pittsburgh Supercomputing Center (PSC). Anton 2 at PSC is supported by the National Institute of General Medical Sciences of the National Institute of Health under Award Number R01GM116961. The Anton 2 machine at PSC was generously made available by D.E. Shaw Research.
Publisher Copyright:
© 2021 Elsevier B.V.
PY - 2022/2/1
Y1 - 2022/2/1
N2 - Here, we perform all-atom molecular dynamics simulations in explicit solvent to study the aggregation of amphipathic peptides into amyloid-like fibrils. We use large simulation boxes containing more than 200,000 atoms and including 50 peptides to account for peptide concentrations of the order of 30 mM. Six different peptide sequences are studied in this work. We show that when long simulations (2–3 μs) are performed, a positive correlation is observed between experiments and simulations. In particular, peptide sequences that do not form fibrils in experiments show a low propensity to form inter-peptide hydrogen bonds and β-structures, and vice versa. Simulations are also performed at different temperatures and NaCl concentration to highlight the importance of hydrophobic and electrostatic interactions on aggregation. The rate of fibril formation in our simulations increases with increasing temperature for amphipathic peptides made from highly hydrophobic amino acids. This phenomena is related to the strength of hydrophobic interactions that enhances with increasing temperature. Electrostatic interactions may be responsible for the preference of anti-parallel β-sheets in our simulations. However, screening these interactions with NaCl favors aggregation of amphipathic peptides made from less hydrophobic amino acids. The sequence of events leading to fibril growth in our simulations is also discussed.
AB - Here, we perform all-atom molecular dynamics simulations in explicit solvent to study the aggregation of amphipathic peptides into amyloid-like fibrils. We use large simulation boxes containing more than 200,000 atoms and including 50 peptides to account for peptide concentrations of the order of 30 mM. Six different peptide sequences are studied in this work. We show that when long simulations (2–3 μs) are performed, a positive correlation is observed between experiments and simulations. In particular, peptide sequences that do not form fibrils in experiments show a low propensity to form inter-peptide hydrogen bonds and β-structures, and vice versa. Simulations are also performed at different temperatures and NaCl concentration to highlight the importance of hydrophobic and electrostatic interactions on aggregation. The rate of fibril formation in our simulations increases with increasing temperature for amphipathic peptides made from highly hydrophobic amino acids. This phenomena is related to the strength of hydrophobic interactions that enhances with increasing temperature. Electrostatic interactions may be responsible for the preference of anti-parallel β-sheets in our simulations. However, screening these interactions with NaCl favors aggregation of amphipathic peptides made from less hydrophobic amino acids. The sequence of events leading to fibril growth in our simulations is also discussed.
KW - Amphipathic peptides
KW - Amyloid
KW - Molecular dynamics
KW - Self-assembly
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U2 - 10.1016/j.molliq.2021.118283
DO - 10.1016/j.molliq.2021.118283
M3 - Article
AN - SCOPUS:85121298537
SN - 0167-7322
VL - 347
JO - Journal of Molecular Liquids
JF - Journal of Molecular Liquids
M1 - 118283
ER -